Relationship between metabolism and biliary excretion of xenobiotics is being studied. The present work focuses on the hepatocarcinogen, N,N-dimethyl-4-aminoazobenzene (DAB, butter yellow). We are determining the quantitative aspect of its metabolism, both in vitro and in vivo, and correlating it with rates of biliary excretion of individual metabolites. Also being studied is the function of liver glutathione (GSH) in the hepato-biliary fate of DAB. In addition to formation of conjugates with primary metabolites of DAB, GSH appears to exert an influence on their formation, particularly with respect to N-demethylation. The quantitative aspect and mechanism of these effects are currently under investigation. The hypolipidemic drug, nafenopin, induces a hyperplastic hepatomegaly. We are currently studying the role(s) of adrenergic receptor mechanisms in the prereplicative changes induced by nafenopin in the rat. Insight into these mechanisms is gained through the use of adrenergic blocking agents and through determination of cyclic nucleotide and cyclic nucleotide-dependent kinases in relation to nafenopin induction. These investigations have been initiated in vivo and are to be extended using primary hepatocyte cultures.